This mid-career investigator award application is designed to support the continued efforts of Dr. Kathleen T. Brady, M.D., Ph.D. in conducting and mentoring patient-oriented drug abuse research. Dr. Brady has been continuously funded to conduct patient-oriented research with substance abusing individuals since completing her psychiatric residency training in 1989. Her particular areas of interest are in psychiatric comorbidity with substance use disorders and the pharmacotherapy of substance use disorders. She is currently funded as the PI on four (Concurrent Treatment of PTSD and Cocaine Dependence, Naltrexone Use in a Community Setting, Sertraline Treatment of Comorbid Alcoholism and PTSD, and Valproate in Relapse Prevention) and the Co-PI on two (Amlodipine in Cocaine Dependence and Buspirone in Methadone Maintained Individuals with GAD) patient-oriented substance abuse research projects. Dr. Brady has a strong track record in mentoring beginning clinical researchers. She is currently the director of the Addiction Psychiatry Fellowship Program and the co-director of a NIDA-funded post-doctoral research fellowship training program. Dr. Brady is a faculty member in the Center for Drug and Alcohol Programs (CDAP) which is an active and productive clinical and research training environment. CDAP provides a variety of education and training-related activities to faculty and students. There are currently eleven faculty at CDAP conducting eighteen funded, patient oriented research projects. The candidate's immediate career goals include the initiation of pilot work to support the competing renewals of existing projects and assisting two junior faculty with the submission of K awards. Her long-term career goals are to continue work in patient-oriented substance abuse research in new directions which build on existing studies. Investigation of CRF antagonists in the treatment of substance use disorders in a clinical setting and the development of a human laboratory model for the measurement of risk-tasking and impulsivity are two areas of preliminary investigation which would be developed during the award period. The candidate would also use the time and funding provided through this award to expand her activities in mentoring fellows and junior faculty in patient-oriented research. This award will allow Dr. Brady to be relieved from a number of clinical and administrative duties in order to refocus her career to center on clinical research and clinical research training activities.